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. 2009 Jun;204(2):335-48.
doi: 10.1007/s00213-009-1465-z. Epub 2009 Jan 20.

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Cristine L Czachowski  1 , Michael J Delory
Affiliations

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Cristine L Czachowski et al. Psychopharmacology (Berl). 2009 Jun.

Abstract

Rationale: Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans.

Objectives: The present experiments utilized a "reinforcer blocking" approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats.

Materials and methods: In "nondependent" experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For "dependent" experiments, rats were made dependent in vapor/inhalation chambers.

Results: Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate's effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats.

Conclusions: The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The "nondependent" paradigm may model early stages of "problem drinking" in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.

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Figures

Fig. 1
Fig. 1
In the ethanol-reinforced group (n=8), mean (±SEM) ethanol intake (g/kg) over days following either saline or acamprosate treatment in nondependent rats. Inset Total mean (±SEM) ethanol intake collapsed over all days. Asterisk indicates a main effect of dose, with the high dose of acamprosate differing from saline
Fig. 2
Fig. 2
In the sucrose-reinforced group (n=8), mean (±SEM) sucrose intake (g/kg) over days following either saline or acamprosate treatment in nondependent rats. Inset Total mean (±SEM) sucrose intake collapsed over all days. Asterisk indicates a main effect of dose, with the high dose of acamprosate differing from saline
Fig. 3
Fig. 3
In the ethanol-reinforced group (n=6), mean (±SEM) ethanol intake (g/kg) over days following either saline or naltrexone treatment in nondependent rats. Inset Total mean (±SEM) ethanol intake collapsed over all days. Asterisks indicates that all doses of naltrexone decreased intake relative to saline, and the high and low doses of naltrexone produced significantly different attenuation of ethanol drinking (number symbol)
Fig. 4
Fig. 4
In the sucrose-reinforced group (n=6), mean (±SEM) sucrose intake (g/kg) over days following either saline or naltrexone treatment in nondependent rats. Inset Total mean (±SEM) sucrose intake collapsed over all days. Asterisks indicates that all doses of naltrexone decreased intake relative to saline, and the high and low doses of naltrexone produced significantly different attenuation of sucrose intake (number symbol)
Fig. 5
Fig. 5
Mean (±SEM) lever-press responses during single, non-reinforced extinction sessions in the ethanol and sucrose groups (as indicated) in acamprosate-treated (left panel) or naltrexone-treated (right panel) nondependent rats. Asterisks indicate a significant difference from the first or collapsed saline treatment conditions; also, the low dose of acamprosate increased the sucrose-seeking response (number symbol)
Fig. 6
Fig. 6
Mean (±SEM) lever-press responses during single, non-reinforced extinction sessions in the ethanol (n=7 both experiments) and sucrose (n=7 experiment 3; n=8 experiment 4) groups as indicated in acamprosate-treated (left panel) or naltrexone-treated (right panel) ethanol-dependent rats. Asterisks indicate a significant difference from the post/saline condition and plus symbol indicates a significant difference from the post/naltrexone condition
See this image and copyright information in PMC

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